1. Field of the Invention
This invention relates to a therapeutic agent for dementia, a method for producing the same, and a method for treating dementia. Specifically, it relates to a therapeutic agent for dementia derived from Hericium ramosum, a method for producing the same and a method for treating dementia using the therapeutic agent for dementia.
2. Description of the Related Art
In recent years, the society is further aging, and the rapid increase in the number of patients with dementia such as Alzheimer-type dementia or cerebrovascular dementia draws attention as a serious social problem. In particular, Alzheimer-type dementia is caused by the degeneration of nerve cells and is characterized by that its symptom proceeds gradually without patients' noticing. Further, because no fundamental therapeutic method has been established yet in the present medical science, the complete recovery is difficult once the disease is developed. Therefore, it is thought to be very important to reduce the risk of the degeneration of nerve cells by a certain active substance, in the stage before the progress of the disease situation or before the development of the disease, or to relief the symptom.
The research and development, such as the elucidation of the mechanism of pathogenesis of Alzheimer-type dementia or the search for a new medicine, are actively conducted. For example, in the brain of a patient with Alzheimer-type dementia, disorders such as the degeneration of neurofibril, the atrophy of nerve cells and the decrease in the nerve cell number are observed, and the pathology corresponds well with the disorder of basal forebrain cholinergic nerve cells, which relates to the memory and the learning ability. Since the nutritional factor for the basal forebrain cholinergic nerve cells is nerve growth factor (NGF), it is thought that the lack of NGF is one of the factors inducing Alzheimer-type dementia. Further, also regarding cerebrovascular dementia, the lack of NGF is thought to be one of the causes thereof.
Here, the neurotrophin family represented by nerve growth factor relates to the functional maintenance of nerve cells. It is thought that dementia such as Alzheimer's disease is caused, when they do not function normally. Since their nutritional factors are proteins, they cannot cross the blood-brain barrier (BBB) and thus cannot be administered orally or by injection. Therefore, it is considered effective for preventing and treating dementia to stimulate astroglia cells, which produce NGF and the like in the brain, to make them produce NGB in the brain.
Regarding a method for accelerating such NGF synthesis in the brain, a natural product of Hericium erinaceum (refer to non-patent document 1, which is expressly incorporated herein by reference in its entirety), which is an edible mushroom classified to Hericiaceae, Hericium, was found to include a hericenone and an erinacine which are the substances to accelerate the NGF synthesis (refer to non-patent document 2, which is expressly incorporated herein by reference in its entirety). Also because the case of Hericium erinaceum was the first case to find a substance which accelerates the NGF synthesis from a natural component except for an animal, the bioactive substances produced by Hericium erinaceum drew a lot of attention, and various studies have been conducted so far.
As an example, according to non-patent document 3, which is expressly incorporated herein by reference in its entirety, it is described that, in an animal experiment with a rat using hericenone C and erinacine A, which are the components derived from Hericium erinaceum, the apparent improvement of the memory retention and the learning ability was observed in the cerebrovascular dementia model, in which the vessel was artificially clogged, as well as in the Alzheimer's disease model.
Here, Hericium ramosum is known as an edible mushroom taxonomically close to Hericium erinaceum, and it is considered that only two species of Hericium ramosum and Hericium erinaceum belong to Hericium. While Hericium erinaceum has been known to bring a metabolic product thereof with a high specificity, Hericium ramosum has been well known to produce a totally different substance group from Hericium erinaceum, though they both belong to Hericiaceae (non-patent document 4, which is expressly incorporated herein by reference in its entirety). Therefore, Hericium ramosum has drawn little attention so far unlike Hericium erinaceum, and it has drawn little attention as a therapeutic agent for dementia.
Regarding the reports on the bioactive substances of Hericium ramosum, there were only a few examples such as a report that erinacine E derived from Hericium ramosum is an agonist for k-opioid receptor while erinacine E derived from Hericium erinaceum has an action to accelerate the nerve growth factor (NGF) production (non-patent document 5, which is expressly incorporated herein by reference in its entirety). That is, few examples which noticed the bioactive substances and functional components contained in Hericium ramosum have been known.